CN102639550B - For the production of low temperature, the single solvent method of sucrose-6-ester - Google Patents
For the production of low temperature, the single solvent method of sucrose-6-ester Download PDFInfo
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- CN102639550B CN102639550B CN201080054223.6A CN201080054223A CN102639550B CN 102639550 B CN102639550 B CN 102639550B CN 201080054223 A CN201080054223 A CN 201080054223A CN 102639550 B CN102639550 B CN 102639550B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/22—Tin compounds
- C07F7/2224—Compounds having one or more tin-oxygen linkages
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
- C07H13/06—Fatty acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/08—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals directly attached to carbocyclic rings
Abstract
The invention discloses a kind of method preparing sucrose-6-ester.In the first step of described method, the sucrose in polar aprotic solvent and organic tin acylation promoter react.Be no more than the temperature removing reaction water of about 80 DEG C.In one aspect, under reduced pressure by distillation fraction polar aprotic solvent except anhydrating.In second step, add carboxylic acid anhydride.In one aspect, the temperature of the reaction mixture obtained below 10 DEG C is kept being enough to the time period of preparing described sucrose-6-ester.Described sucrose-6-ester can be converted into trichlorogalacto-sucrose.
Description
Technical field
The present invention relates to sucrose-6-ester and prepare the method for sucrose-6-ester.Particularly, the present invention relates to the method preparing sucrose-6-ester, in the process, remove the water of dereaction in the temperature being no more than about 80 DEG C.
Background technology
Trichlorogalacto-sucrose (4,1 ', 6 '-three chloro-4,1 ', 6 '-three deoxidation sucralose (galactosucrose)), i.e. a kind of high intensity sweetner that can be used in the application of multiple F&B is a kind of sucralose with following molecular structure:
Trichlorogalacto-sucrose
Trichlorogalacto-sucrose is passed through the conversion of hydroxyl of 4,1 ' and 6 ' position to be that chloro obtains by sucrose.In this course, be reversion at the three-dimensional chemical configuration of 4.
Preparing in the method for trichlorogalacto-sucrose a kind of by sucrose, is first sucrose-6-ester by sucrose inversion, such as cane sugar-6-acetic ester or Sucrose-6-benzoate.By reacting with chlorizating agent and teritary amide, by sucrose-6-ester chlorination, and gained reaction mixture being heated, using alkali aqueous solution quencher subsequently.To obtain 4,1 ', 6 '-three chloro-4,1 ', 6 '-three deoxidation sucralose ester (trichlorogalacto-sucrose-6-ester) is converted into trichlorogalacto-sucrose, is purified by trichlorogalacto-sucrose subsequently and is separated.
Sankey, United States Patent (USP) 5,470,969; Vernon, EP0475619; Clark, United States Patent (USP) 6,939,962; And White, EP0776903, disclose the method for synthesis of sucrose-6-esters, disclosed in it, content is combined in this all by reference.Disclosed in Clark, method comprises: (a) is in a kind of polar aprotic solvent; such as N; in dinethylformamide; sucrose and organic tin acylation promoter are reacted; add constantly can by condistillation except the non-polar co-solvent of anhydrating simultaneously; and by condistillation except anhydrating; thus the reaction mixture being substantially free of water is provided; then (b) adds carboxylic acid anhydride in described reaction mixture, and is incubated by the reaction mixture obtained and keeps being enough to the time period of preparing sucrose-6-ester.Typical described non-polar co-solvent is hydrocarbon, such as hexanaphthene, n-heptane, toluene or octane-iso.
This method needs a large amount of non-polar co-solvent, must carry out drying before interpolation to described non-polar co-solvent, then in order to recycle, must reclaim and dry described non-polar co-solvent again.Step (a) can be decomposed in the temperature province in (even if when reaction times of relatively short only 20-30 minute) at carbohydrate and carried out.Because described non-polar co-solvent can cause the precipitation of sucrose, so the existence of non-polar co-solvent limits the maximum sucrose concentration that can use in this process.In addition, the unreacted sucrose remained in sucrose-6-ester product can produce in follow-up chlorinating step undesirably obtain and be difficult to remove tetrachloride.Therefore, the method being formed sucrose-6-ester by sucrose not having these shortcomings is needed.
Micinski, PCT public announcement of a patent application WO2008/084197, discloses a kind of method of synthesis of sucrose-6-esters, comprising: (a) forms the first reaction mixture, it comprises sucrose, polar aprotic solvent such as DMF and organic tin acylation promoter; B () is being enough to provide the temperature of substantially water-free second reaction mixture, pressure and under the residence time, by in a kind of mode of continuous countercurrent, by described first reaction mixture with can contact except the gas anhydrated or solvent vapour, therefrom except anhydrating; Then (c) adds carboxylic acid anhydride in described second reaction mixture, to obtain the 3rd reaction mixture, and is incubated by described 3rd reaction mixture and keeps being enough to the time of preparing sucrose-6-ester.
This method needs use can except the gas anhydrated or solvent vapour.According to the present invention, have been surprisingly found that, use and can there is no need except the gas anhydrated or solvent vapour, and achieve the more easy method of one.
Summary of the invention
The present invention is a kind of method of producing sucrose-6-ester.In one aspect, the present invention is a kind of method, and described method comprises the following steps: in order
A () provides the first reaction mixture, described first reaction mixture comprises sucrose, polar aprotic solvent and organic tin acylation promoter;
(b) from described first reaction mixture except anhydrating, to provide substantially water-free second reaction mixture, and
C () adds carboxylic acid anhydride in described second reaction mixture, to provide the 3rd reaction mixture, thus prepare sucrose-6-ester;
Wherein:
Non-polar co-solvent is not added in step (b) period; And
In step (b), temperature is no more than about 80 DEG C.
In one aspect of the invention, in step (b) period, by under reduced pressure distilled water and described polar aprotic solvent, thus except anhydrating.In one aspect of the invention; in step (a) and (b), described first reaction mixture and/or described second reaction mixture are made up of sucrose, polar aprotic solvent, organic tin acylation promoter and/or their reaction product substantially.In one aspect of the invention, described organic tin acylation promoter is 1,3-diacetoxy-1,1,3,3-tetrabutyldistannoxane (distannoxane diacetate esters or DSDA).In one aspect of the invention, described polar aprotic solvent is DMF.In one aspect of the invention, described carboxylic acid anhydride is diacetyl oxide and described sucrose-6-ester is cane sugar-6-acetic ester.In one aspect of the invention, step (c) is carried out below 10 DEG C.
In step (b), rapidly and effectively removes the water formed by sucrose and the reaction of organic tin acylation promoter.Because at the water of temperature low compared with the method in past except dereaction, even if so when using the reaction times extended, the decomposition amount of carbohydrate also obviously reduces.But, even if because described reaction is also carried out very efficiently at reduced temperatures, therefore extend reaction times unnecessary.Typically, the reaction times is at most 60 minutes, or is at most 45 minutes, or is at most 30 minutes, or is at most 20 minutes.Typically, need the reaction times being at least 5 minutes, and it should be understood that the required definite time will depend on temperature, the vacuum tightness of use and the speed of liquid surface area new in the reaction exposure.
Using non-polar solvent because unnecessary to remove water, therefore avoiding to add non-polar co-solvent except anhydrating completely.This makes technique be simplified, and reclaims the non-polar co-solvent a large amount of with drying because unnecessary subsequently in order to reuse.Because compared with the method in past, present method is carried out in higher concentrations and is employed different from the method for anhydrating, and the heat for reacting by heating mixture is less, and this just creates the saving on cost of energy.In addition, in lower temperature, described reaction has higher selectivity, decomposes hardly, which increases the ultimate production of described trichlorogalacto-sucrose preparation method.Implement this method also more economically, because can use the sucrose of high density, the possibility of sucrose pellet reduces in this method, and can carry out described method with more small-sized thus more cheap equipment.
In addition, need not use and except the gas anhydrated or solvent vapour, more easy method can be result in.Therefore, according to the present invention, in step (b), described mixture preferably not with can contact except the gas anhydrated or solvent vapour.Particularly, in step (b), described mixture preferably not with the mode of continuous countercurrent with can contact except the gas anhydrated or solvent vapour.
Accompanying drawing explanation
Fig. 1 is process flow sheet, shows the low temperature single solvent method of producing sucrose-6-ester.。
Specific embodiments
Unless indicated in addition at context, in the specification and in the claims, the term of organic tin acylation promoter, polar aprotic solvent, carboxylic acid anhydride, non-polar co-solvent and similar term all comprise the mixture of these materials.Except as otherwise noted, all percentage ratio be weight percentage and all temperature all in DEG C (centigradetemperature).Decompression refers to subatmospheric pressure.Temperature refers to the temperature of correlated response mixture, namely the internal temperature of liquid phase is (in order to avoid ambiguity, temperature does not refer to heat source temperature, heat source temperature is usually above by the internal temperature of reaction mixture heated, temperature does not refer to the temperature of cooling source yet, and cooling source temperature is usually less than the temperature of cooled reaction mixture).The temperature reduced refers to the temperature lower than the particular polarity aprotic solvent boiling point existed in reaction mixture under atmospheric pressure.
The method being prepared trichlorogalacto-sucrose by sucrose comprises the following steps.First, with ester group, such as acetic ester or benzoic ether, be enclosed in the activity hydroxy of sucrose 6.By 4 of the sucrose-6-ester of acquisition, the conversion of hydroxyl of 1 ' position and 6 ' position is chloro, the three-dimensional chemical configuration reversion of 4.Subsequently by 6 ester group removings of the trichlorogalacto-sucrose-6-ester of gained, and purify and be separated the product trichlorogalacto-sucrose obtained.Described method or its independent step can be all batch processes or continuation method.
The preparation of sucrose-6-ester
Under existing at organic tin acylation promoter; in anhydrous polar aprotic solvent; under reaction conditions described herein; in certain temperature and the time being enough to generation sucrose-6-ester; the carboxylic acid anhydride of sucrose with such as diacetyl oxide or benzoyl oxide is reacted, can to sucrose 6 hydroxyl selective protections.The hydroxyl that described 6 ester groups protect at 6 does not carry out chlorination reaction.Therefore, it is possible to use any under the condition of chlorination reaction stable and can not affect obtain the condition of trichlorogalacto-sucrose under the ester group that is removed.When preparing sucrose-6-ester, such as, 1,3-diacetoxy-1,1,3,3-tetrabutyldistannoxane can be used as organic tin acylation promoter, and use diacetyl oxide as carboxylic acid anhydride.Such as O ' Brien, U.S.Pat.No.4,783,526; Navia, U.S.Pat.No.4,950,746; Simpson, U.S.Pat.No.4,889,928; Neiditch, U.S.Pat.No.5,023,329; Walkup, U.S.Pat.No.5,089,608; Vernon, U.S.Pat.No.5,034,551; Sankey, U.S.Pat.No.5,470,969; Kahn, U.S.Pat.No.5,440,026; Clark, U.S.Pat.No.6,939,962, and Li, U.S.Pat.Pub.2007/0227897A1 disclose the preparation of sucrose-6-ester, disclosed in it, content is combined in this by reference.
The typical case of sucrose-6-ester prepares use two-step approach.The first step, in a solvent, contacts sucrose with organic tin acylation promoter, and removes, reaction water to form tin-sucrose adducts.Subsequently, the reaction mixture containing tin-sucrose adducts is contacted with carboxylic acid anhydride.Sucrose-6-ester can be separated from the reaction mixture obtained.Alternatively, organic tin acylation promoter and/or its reaction product can be separated from reaction mixture, and the sucrose-6-ester solution in polar aprotic solvent obtained is used for next step, and by 4, the conversion of hydroxyl of 1 ' position and 6 ' position is chloro.
To the sucralose product solubleness in a solvent of tin that the selection of polar aprotic solvent depends primarily on sucrose, organic tin acylation promoter and obtains, also security and toxicity to be considered.The boiling point of described polar aprotic solvent is preferably higher than the boiling point of water under normal atmosphere.The boiling point of described polar aprotic solvent is more preferably than the boiling point height at least 50 DEG C of water under normal atmosphere.The polar aprotic solvent be applicable to is, such as, and METHYLPYRROLIDONE, dimethyl sulfoxide (DMSO), N,N-dimethylacetamide, hexamethylphosphoramide, N, N-diethylformamide, N, N-diethyl acetamide, and be preferably DMF.
The consumption of polar aprotic solvent also will depend primarily on above-mentioned solubleness factor.Generally, it should be noted that according to the amount of polar aprotic solvent required for the present invention can typically be less than add non-polar co-solvent prior art system in amount.This is because the solubleness of reactive component is reduced by the existence of non-polar co-solvent in solvent system, to such an extent as to need a large amount of polar aprotic solvent to keep the reactive component in solution.Therefore, when not existing according to non-polar co-solvent of the present invention, need to use less polar aprotic solvent.This provide the advantage of reaction mixture in downstream process process, that also provide economic aspect with advantage that is environment aspect.When polar aprotic solvent is DMF, every lg sucrose can typically use about 4g to about 22g polar aprotic solvent, and every lg sucrose preferably uses about 7g to about 16g polar aprotic solvent.
Organic tin acylation promoter can be any well known in the art those, such as, any at Navia, U.S.Pat.No.4,950,746; Neiditch, U.S.Pat.No.5,023,329; Walkup, U.S.Pat.No.5,089,608; And/or the acylation promoter of organic tin disclosed in Vernon, EP-0475619-A, disclosed in it, content is combined in this by reference.Exactly, organic tin acylation promoter can be: 1,3-bis-(-oxyl)-1,1,3,3-tetra--(alkyl) distannoxane; Two (alkyl) stannic oxide; Two (alkyl) stannic oxide and divalent alcohol, alkanolamine or can the reaction product of alpha-alcohol ketone of enolization; 1,3-bis-acyloxy-1,1,3,3-tetra--(alkyl) distannoxane; 1-(acyloxy)-3-hydroxyl-1,1,3,3-tetra--(alkyl) distannoxane.The example of a rear class acylation promoter is 1-acetoxy-3-hydroxyl-1,1,3,3-tetrabutyldistannoxane.Term " alkyl " refers to alkyl, cycloalkyl, aryl, aromatic alkyl group.Organic tin acylation promoter is preferably 1,3-bis-acyloxy-1,1,3,3-tetra--(alkyl) distannoxane.
When described organic tin acylation promoter is 1,3-bis-(-oxyl)-1,1,3,3-tetra--(alkyl) distannoxane, described hydrocarbonoxy radical is preferably C
1-C
8alkoxy base or phenoxy group group, be more preferably methoxyl group, oxyethyl group, positive propoxy, n-butoxy, n-pentyloxy or positive hexyloxy, most preferably be methoxy group.Hydrocarbyl group and then preferably alkyl, be more preferably C
1-C
8alkyl, most preferably be normal-butyl.
When described organic tin acylation promoter is two (alkyl) stannic oxide, described alkyl is preferably alkyl, is more preferably C
1-C
8alkyl, most preferably is normal-butyl.
When described organic tin acylation promoter be two (alkyl) stannic oxide and divalent alcohol, alkanolamine or can the reaction product of alpha-alcohol ketone of enolization time, two (alkyl) stannic oxide is carried out preferably as above-mentioned.Described divalent alcohol can be alkanediol, and it preferably has 2 to 8 carbon atoms.The example be applicable to is ethylene glycol, 2, ammediol, 2,3-butanediol, 1,3 butylene glycol, BDO, 1,3-PD, 1,2-pentanediol and 1,2-hexylene glycol.Or divalent alcohol can be cycloalkanes glycol, and it preferably has 5 to 8 carbon atoms.The example be applicable to is 1,2-cyclohexane diol and 1,2-pentamethylene glycol.In all cases, apartly in the carbochain that preferably two hydroxyls combine at them be no more than four carbon atom, more preferably they are on adjacent carbons or in conjunction with atom separation carbon atom of hydroxyl.Described alkanolamine is preferably C
2-C
8alkanolamine, apartly in the carbochain that preferred hydroxyl and amido combine at them is no more than four carbon atom, and more preferably hydroxyl and amido are on adjacent carbons or in conjunction with atom separation carbon atom of hydroxyl and amido.The alkanolamine be applicable to is thanomin, 2-amino-1-propyl alcohol and 1-amino-2-propyl alcohol.The alpha-alcohol ketone of the enolization be applicable to is 2-hydroxyl-2-phenyl acetophenone and 3-hydroxy-2-butanone.
In certain embodiments, organic tin acylation promoter is 1,3-bis-acyloxy-1,1,3,3-tetra--(alkyl) distannoxane.The alkyl of 1,3-bis-acyloxy-1,1,3,3-tetra--(alkyl) distannoxane is preferably alkyl, is more preferably C
1-C
8alkyl, most preferably is butyl, so 1,1,3,3-tetrabutyldistannoxane is particularly preferred.Suitable is the acyloxy that acyloxy mates the carboxylic acid anhydride that will use, and therefore such as, when preparing sucrose-6-ester, 1,3-diacetoxy-1,1,3,3-tetrabutyldistannoxane (distannoxane diacetate esters or DSDA) is highly preferred.Above-mentioned alkyl and acyloxy are also preferred in use 1-acyloxy-3-hydroxyl-1,1,3,3-tetra--(alkyl) distannoxane is as the situation of organic tin acylation promoter.
When organic tin acylation promoter is nuclear species (such as the distannoxane) comprising two tin atoms in each molecule; preferably there is every mole of sucrose 0.5 to 2.5 molar equivalent in the reactive mixture; be more preferably 0.75 to 1.2 molar equivalent; be more preferably 0.9 to 1.1 molar equivalent, most preferably be the acylation promoter of 1.0 molar equivalents.When organic tin acylation promoter is mononuclear species (such as two (alkyl) stannic oxide) comprising a tin atom; preferably there is every mole of sucrose 0.5 to 2.5 molar equivalent in the reactive mixture; be more preferably 0.8 to 1.5 molar equivalent, most preferably be the acylation promoter of 1.2 molar equivalents.
In the first step (step (a)), the first reaction mixture comprising the sucrose be in polar aprotic solvent, by sucrose dissolved is obtained in polar aprotic solvent, is typically DMF.Mild heat dissolving saccharose can be utilized.Subsequently organic tin acylation promoter is added reaction mixture.Subsequently, in step (b), in one aspect of the invention, by underpressure distillation, except anhydrating and polar aprotic solvent at least partially from the first reaction mixture.Polar aprotic solvent steam removes the water of reaction, and driving a reaction carries out to the direction of sucrose tin adducts in a very effective manner, thus provides the second reaction mixture.
Interpolation can by condistillation except the non-polar co-solvent of anhydrating, such as, at Sankey, U.S.Pat.No.5, and 470,969; White, EP0776903; And the solubility promoter described in Vernon, EP0475619, this way is unnecessary for the water effectively except dereaction, and disclosed in above-mentioned document, content is combined in this by reference.Therefore, in the present invention, do not add non-polar co-solvent to react.This kind solvent is typically the solvent not carrying out with polar aprotic solvent, organic tin acylation promoter or sucrose reacting; The solvent of mixture is generated with polar aprotic solvent, organic tin acylation promoter, sucrose; Be about 75 DEG C to about 153 DEG C in scope, be preferably solvent lower than the internal reaction temperature backflow of 100 DEG C; With the solvent of water condistillation; And do not cause the insoluble solvent of sucrose.This kind solvent is typically and can not mixes with water and to form those of the minimum boiling point azeotrope of constant composition with water, such as stable hydrocarbon, aromatic hydrocarbons, hydrochloric ether, ketone and ether.The example of this kind solvent comprises hexanaphthene, normal heptane, toluene and octane-iso (pure isooctane).In another aspect of the present invention; dewatered by underpressure distillation and the first reaction mixture formed after at least eliminating segment polarity aprotic solvent and the second reaction mixture, to be preferably substantially made up of sucrose, polar aprotic solvent, organic tin acylation promoter and/or their reaction product.
In the distillating method of this embodiment of step (b), different with the method in Micinski, PCT public announcement of a patent application WO2008/084197, preferably except polar aprotic solvent itself, do not use the gas or solvent vapour that can dewater.Therefore, in step (b), mixture preferably except contacting with polar aprotic solvent itself, does not contact with the gas that can dewater or solvent vapour.The example of the gas used in the method for Micinski is nitrogen, argon gas, air, helium and carbonic acid gas.The example of the solvent vapour class used in the method for Micinski is stable hydrocarbon, aromatic hydrocarbons, hydrochloric ether, ketone, ester and ether.The object lesson of solution vapor is hexanaphthene, normal heptane, octane-iso (pure isooctane), benzene, toluene, diethyl ether, chloroform, tetracol phenixin, hexane, ethyl acetate and methyl acetate.Preferred hydrocarbons, and particularly preferably hexanaphthene, normal heptane, toluene and octane-iso (pure isooctane).
In step (b), i.e., in the removing of water and polar aprotic solvent at least partially, polar aprotic solvent, in decompression, is namely removed under subatmospheric pressure.Also use the temperature of reduction, namely lower than the temperature of the boiling point of polar aprotic solvent under atmospheric pressure.The temperature of reaction mixture lower than 80 DEG C, or between lower than 80 DEG C to about 0 DEG C.Removing polar aprotic solvent process in, the temperature of the first reaction mixture preferably more than about 80 DEG C, about 78 DEG C, about 75 DEG C or about 70 DEG C.In other embodiments, in the process of removing polar aprotic solvent, the temperature of reaction mixture is in a first step lower than 60 DEG C or lower than 50 DEG C.Preferably, in the process of removing polar aprotic solvent, the temperature of the first reaction mixture is maintained at about between 80 DEG C to about 0 DEG C, between about 78 DEG C to about 5 DEG C, between about 75 DEG C to about 10 DEG C, or between about 70 DEG C to about 15 DEG C.
Can by temperature described in pressure-controlling residing during control removing polar aprotic solvent.In the process of removing polar aprotic solvent, preferred pressure is between about 65mmHg (about 8.7kPa) to about 0.5mmHg (about 0.1kPa), between about 50mmHg (about 6.7kPa) to about 15mmHg (about 2.0kPa), or between about 40mmHg (about 5.3kPa) to about 20mmHg (about 2.7kPa).
By using described method, compare method in the past can complete reaction water removing in obvious lower temperature.Even if described lower temperature causes extending the reaction times, the decomposition of carbohydrate is also obviously lower.But, even if because described reaction is also carried out very efficiently at reduced temperatures, therefore extend reaction times unnecessary.Except the water of dereaction also completes under the condition not adding non-polar co-solvent.Compared to the more black material produced by additive method, products obtained therefrom stream is the product of clarification, very slight jaundice.
Those skilled in the art easily know; by adding the solution of organic tin acylation promoter in apolar aprotic solvent; by organic tin acylation promoter introduce reaction mixture, described non-polar co-solvent be such as above-mentioned discussion can by condistillation except one of non-polar co-solvent of anhydrating.Such as, organic tin acylation promoter can be added the reaction mixture in cyclohexane solution.Therefore (30% (w/w) of reaction media thing is such as less than on a small quantity, be less than 20% (w/w), being less than 15% (w/w), or being less than 10% (w/w)) apolar aprotic solvent can be present in reaction mixture when step (a) starts.As being apparent that for technician, the amount of non-polar co-solvent low like this helps to dewater required amount far below in art methods.Reduce pressure when distilling and starting removing described a small amount of non-polar co-solvent subsequently.Decompression and except anhydrate and polar aprotic solvent at least partially temperature under distillation during (namely during step (b)), in reaction mixture, do not add additional non-polar co-solvent.In certain embodiments, such as, when adding organic tin acylation promoter in solid form, reaction mixture may be slurry form when step (b) starts.Subsequently, when reaction is carried out, reaction mixture becomes uniform.This is applicable to particularly when organic tin acylation promoter is two (alkyl) stannic oxide, such as, time Dibutyltin oxide (DBTO).
Except after the water of dereaction in step (b), in next step (step (c)), the solution of the sucrose-tin adduct produced in step (b) is being near or below room temperature cooling, and with the esterifying agent be applicable to, such as carboxylic acid anhydride mixing, to generate the 3rd reaction mixture.Described 3rd reaction mixture is preferably maintained in the range of from about less than 10 DEG C, continues the time being enough to prepare sucrose-6-ester.Even if lower than 20 DEG C, reaction also occurs rapidly.If necessary, can add a small amount of non-proton solubility promoter in step (c), such as hydro carbons is as hexanaphthene, to keep the material in solution.Should by any after step (b) and before step (c)/solvent seasoning that adds of period, thus carboxylic acid anhydride is not hydrolyzed to its corresponding carboxylic acid.
The add-on of carboxylic acid is preferably 0.8 to 1.5 molar equivalent (every mole of sucrose parent material), is more preferably from 1.05 to 1.35 molar equivalents, is also more preferably 1.1 to 1.25 molar equivalents, most preferably be 1.15 molar equivalents.Too much carboxylic acid anhydride generates the sucrose (i.e. the formation of diester, three esters etc.) of excessive excessive carboxylation.Very few carboxylic acid anhydride produces unreacted sucrose.
If can use applicable carboxylic acid anhydride, present method can be used for preparing various sucrose-6-ester.Such as, by using diacetyl oxide, present method can be used for preparing cane sugar-6-acetic ester; By using benzoyl oxide, Sucrose-6-benzoate can be prepared; By using acrylic anhydride, sucrose-6-methacrylic ester can be prepared; By using propionic anhydride, sucrose-6-propionic ester can be prepared; By using butyryl oxide, sucrose-6-butyric ester can be prepared; Deng.
Being near or below the temperature of room temperature (i.e. surrounding environment) after the time of abundance, by the quencher of described mixture water.After reaction process, such as, high pressure liquid chromatography can be carried out.
Organic tin acylation promoter can use at separation sucrose-6-ester Posterior circle.The method of recovery and reuse organic tin acylation promoter is disclosed in Vernon, and United States Patent (USP) 5,034,551, disclosed in it, content is combined in this by reference.When organic tin acylation promoter is 1,3-bis-acyloxy-1,1,3,3-tetra--(alkyl) distannoxane, preferably reclaims after step (c) and recycle.A small amount of water is added reaction mixture after step (c), if be necessary, add a small amount of apolar aprotic solvent simultaneously and typically be hexanaphthene.Described reaction mixture distributes between water and apolar aprotic solvent, form upper strata (i.e. low density) phase, containing 1,3-bis-acyloxy-1,1,3,3-, tetra--(alkyl) distannoxane and apolar aprotic solvent, and lower floor's (i.e. high-density) phase, containing sucrose-6-ester; Polar aprotic solvent, such as, DMF; Water; And carboxylic acid.Remove described upper strata phase, and use apolar aprotic solvent to extract lower floor's phase.Polar aprotic solvent extract is merged and preferably under reduced pressure concentrates and use alcohol Ficus caricaL.1,3-bis-acyloxy-1,1,3,3-tetra--(alkyl) distannoxane reclaimed is purified further by conventional techniques.
Sucrose-6-ester, carboxylic acid (carboxylic acid formed by the reaction of carboxylic acid anhydride and sucrose add any can by the carboxylic acid formed excessive anhydride hydrolyzes with the water added), unreacted sucrose, on a small quantity other sucrose ester and polar aprotic solvent are contained in described lower floor.Preferably before further process sucrose-6-ester, carboxylic acid is removed from the solution of sucrose-6-ester polar aprotic solvent.When described acid be relative volatility as acetic acid time, can be removed, such as, by vacuum fractionation, with except anhydrating, any remaining apolar aprotic solvent and carboxylic acid.During distilling or afterwards, supplementary polar aprotic solvent can be added, if particularly by when being further processed in same solvent is as DMF the mixture comprising sucrose-6-ester obtained.Described sucrose-6-ester in the polar aprotic solvent of remnants can be directly used in, and such as, at Walkup, United States Patent (USP) 4,980, chlorination process disclosed in 463, disclosed in it, content is combined in this by reference.Optionally, by program such as crystallization process recovery sucrose-6-ester from solvent such as methyl alcohol of routine, and chlorination process is used it for.
Can highly selective and high yield ground obtain sucrose-6-ester.When sucrose-6-ester is cane sugar-6-acetic ester, the selectivity of these 6 monoacetates can be very high, and the selectivity that the standardized assays of 6 monoacetates obtains is up to the 85-90% of whole carbohydrate.Can produce in chlorinating step and undesirably to occur and the unreacted sucrose of tetrachloride being difficult to remove can be reduced to < 0.1%.
Described method can be implemented with simple batch process form.Alternatively, described method can form be implemented in a batch process, and wherein, polar aprotic solvent is added continually and removes, and in for some time subsequently, polar aprotic solvent is removed but does not add additional polar aprotic solvent.
Alternatively, the method for the invention can be implemented with continuous processing form.
Shown in Figure 1 according to an embodiment of the method for the invention.With reference to Fig. 1, the solution comprising sucrose (usually about 8-10%) in polar aprotic solvent such as DMF is added container (10).Also add organic tin acylation promoter, as 1,3-diacetoxy-1,1,3,3-tetrabutyldistannoxane (DSDA).
Vacuum is maintained by vacuum pump (12).The steam of polar aprotic solvent is by condenser (14) condensation.
Select the pressure in container (10), make the temperature of reaction mixture be no more than required temperature, less than 80 DEG C according to appointment.For those skilled in the art obviously, by reducing the pressure in container (10), the temperature of reaction mixture can be adjusted to lower than 80 DEG C.External heat exchanger (16) can be passed through by heat input pod (10).Alternatively or additionally, by heating jacket (the not illustrating in the drawings) heat supply on container (10), to container (10) input heat.
From container (10) bottom, Commodity flow is introduced reactor, as previously mentioned, in this place cooling also acidylate.Can use any ordinary method that Commodity flow is filled with acylation reaction device, such as, use recycle pump (18).
In unshowned alternative embodiment, the dry steam of polar aprotic solvent can generate alone and be fed to container (10).This by allow denseer sucrose in polar aprotic solvent solution feed to container (10).Denseer solution will reduce the liquid load of container (10), improve mean residence time simultaneously.
Importantly, the raw material of esterification is very dry.If needed, additional water removal phase (not shown) can be used before esterification.Such as, small size single stage flashing component can be inserted between container (10) and acylation reaction device, to remove any minor amount of water that may be introduced into process.
Sucrose-6-ester is to the conversion of trichlorogalacto-sucrose-6-ester
In order to sucrose-6-ester being converted into trichlorogalacto-sucrose-6-ester, by 4 of sucrose-6-ester, the conversion of hydroxyl of 1 ' position and 6 ' position is chloro, and the three-dimensional chemical configuration reversion of 4.By 4 of ester, the conversion of hydroxyl of 1 ' position and 6 ' position is chloro and is disclosed in Walkup, U.S.Pat.No.4,980,463 in the method for the three-dimensional chemical configuration reversion of 4; Jai, U.S.Pat.Pub.2006/0205936A1; With in Fry, U.S.Pat.Pub.2007/0100139A1, disclosed in it, content is combined in this by reference.
This chlorination method comprises the following steps.The reaction mixture of the chlorizating agent of preparation containing sucrose-6-ester, teritary amide and at least seven molar equivalents.Such as, in a method, sucrose-6-ester can be added feedstream, its containing have an appointment 20 % by weight to about 40 % by weight sucrose-6-ester.Can be about 5: 1 to about 12: 1 relative to the weight ratio of the teritary amide of carbohydrate whole in reaction mixture.Alternatively, the chloroformyl inferior amine salt (chloroformiminiumsalt) of preprocessing can be used, such as (chlorine methylene radical) alkyl dimethyl ammonium chloride (Arnold reagent).(chlorine methylene radical) alkyl dimethyl ammonium chloride reacts by such as phosgene and DMF to be prepared.Typically the mol ratio of (chlorine methylene radical) alkyl dimethyl ammonium chloride and sucrose-6-ester is about 7: 1 to about 11: 1.
Subsequently, by 2 of sucrose-6-ester, 3,4,1 ' position, 3 ' position, 4 ' position and 6 ' position conversion of hydroxyl be O-alkyl inferior amine salt group.The product obtained is enough in certain temperature or some heating temperatures one section or several sections the time generating product, and described product comprises the derivative of trichlorogalacto-sucrose-6-ester, and in described derivative, remaining hydroxyl is retained with O-alkyl inferior amine salt group.Such as, Walkup, U.S.Pat.No.4,980,463, disclosed in it, content is combined in this by reference, and Fry, U.S.2007/0100139, and content disclosed in it combines by reference and disclosed herein is such method.
Due to formed chloroformyl inferior amine salt or Vilsmeier reagent dispensable for chlorination reaction, so chlorizating agent refers to any compound that can be used in generating chloroformyl inferior amine salt or Vilsmeier reagent, maybe the conversion of hydroxyl of sucrose-6-ester can be become the compound of chloro.Some can react with teritary amide the chlorizating agent forming chloroformyl inferior amine salt and comprise: such as phosgene, phosphoryl chloride, phosphorus pentachloride, thionyl chloride, sulfuryl chloride, oxalyl chloride, superpalite (" trichloromethylchloroformate "), two (trichloromethyl) ester (" triphosgene ") of carbonic acid, and methylsulfonyl chloride.Available teritary amide comprises: such as, DMF (DMF), N-formyl piperidine, N-formyl morpholine and N, N-diethylformamide.When using DMF as teritary amide, reaction solvent also can be it can be used as to use.The solubility promoter used can reach about 80 more than volume % of the liquid phase of reaction media.Available solubility promoter, for being chemically inert, can provide enough dissolving poweies again, make reaction the monochlorinated stage be substantially uniform those, such as toluene, o-Xylol, 1,1,2-trichloroethane, 1,2-diethoxyethane and diglyme.
By described reaction mixture quencher, make 2,3, the hydroxyl of 3 ' position and 4 ' position recovers, and form trichlorogalacto-sucrose-6-ester.Described reaction mixture by adding alkali quencher, described alkali relative to the amount of chlorizating agent used in reaction for about 0.5 to about 2.0 molar equivalent, typical case about 1.0 are to about 1.5 molar equivalents.Alkali metal hydroxide, the aqueous solution of such as sodium hydroxide or potassium hydroxide; Alkaline earth metal hydroxides, the aqueous slurry of such as calcium hydroxide; Or ammonium hydroxide aqueous solution all can be used for reacting quencher.Such as, can use the aqueous solution of alkali metal hydroxide, as aqueous sodium hydroxide solution, its content is about 5 % by weight to about 35 % by weight, is typically about 8 % by weight to about 20 % by weight, is preferably about 10 % by weight to about 12 % by weight.
As mentioned below, by adding alkali in reaction mixture, quencher can be carried out by double stream process or by circulation method.In respective situation, all control ph and temperature in the process of adding alkali.Typical case in pH value for about 8.5 to about between 10.5 and temperature performs quencher between about 0 DEG C to about 60 DEG C.In quencher reaction process, preferably do not allow pH value to exceed about 10.5.
In double stream process, implement quencher by slowly adding alkali aqueous solution and slowly add chlorination reaction material in reaction vessel simultaneously.Chlorination reaction mixture and alkali aqueous solution are slowly added, until add the chlorination reaction mixture of desired amount simultaneously.Add the aqueous solution of other alkali until reach the pH value of expection.Subsequently, for remaining reaction, temperature and pH value are remained on expection level.Described method can be batch processes or continuation method.
In circulation method, by chlorination reaction mixture is implemented quencher from container by recycle loop.Chlorination reaction mixture and alkali aqueous solution are slowly added described circulation loop.Add enough alkali aqueous solutions, until reach the pH value of expection.Subsequently, for remaining reaction, temperature and pH value are remained on expection level.Described method can be batch processes or continuation method.
After quencher, by adding aqueous acid example hydrochloric acid aqueous solution neutralization reaction mixture.The mixture obtained is comprise trichlorogalacto-sucrose-6-ester, other carbohydrate in the aqueous solvent of water at primary solvent, comprises the carbohydrate impurity of chlorination, unreacted teritary amide and salt.
Trichlorogalacto-sucrose-6-ester is to the conversion of trichlorogalacto-sucrose
The mixture typical case of described acquisition comprises trichlorogalacto-sucrose and trichlorogalacto-sucrose-6-ester.The mixture of described trichlorogalacto-sucrose and trichlorogalacto-sucrose-6-ester can be converted into trichlorogalacto-sucrose, and purifies by means commonly known in the art and be separated the trichlorogalacto-sucrose obtained.The method of hydrolysis trichlorogalacto-sucrose-6-ester, separation trichlorogalacto-sucrose and/or purification trichlorogalacto-sucrose is disclosed in such as Catani, U.S.Pat.Nos.5,977,349,6,943,248,6,998,480 and 7,049,435; Vernon, U.S.Pat.No.6,890,581; EIKabbani, U.S.Pat.Nos.6,809,198 and 6,646,121; Navia, U.S.Pat.Nos.5,298,611 and 5,498,709 and U.S.Pat.Pub.2004/0030124; Liesen, U.S.Pat.Pub.2006/0188629A1; Fry, U.S.Pat.Pub.2006/0276639A1; EIKabbani, U.S.Pat.Pub.2007/0015916A1; Deshpande, U.S.Pat.Pub.2007/0160732A1; With in Ratnam, U.S.Pat.Pub.2007/0270583A1, disclosed in it, content is combined in this by reference.
Such as; a () and can be enough to blocking group to remove the time in certain temperature; be trichlorogalacto-sucrose by the pH value of reaction mixture being increased to about 11 ± 1 by trichlorogalacto-sucrose-6-Ester hydrolysis, and (b) is by such as steam stripped removing teritary amide.First perform (a) or (b).By continuing counter-current extraction mixture to reclaim trichlorogalacto-sucrose from gained mixture in batches, continuously or with organic solvent, described organic solvent is such as methylene dichloride, chloroform, 2-butanone, pimelinketone, ethyl acetate or its mixture.Can decolour to described organic extract carbon, concentrate and precipitate trichlorogalacto-sucrose by adding trichlorogalacto-sucrose kind crystalline substance.By recrystallize from such as water or ethyl acetate, can the crystals of sucralose obtained be purified further.Alternatively, by chromatographic purification sucrose.By preliminary using non-crystallization purification method as solvent extration or chromatography, succeeded by the continuous print crystallisation step from such as water or ethyl acetate of more than three times, and by the Recycling Mother Solution that remains from each crystallisation step to the raw material of other crystallization or purification step, and trichlorogalacto-sucrose of purifying, be also applicable.
Alternatively, the conversion of trichlorogalacto-sucrose-6-ester to trichlorogalacto-sucrose can be carried out in containing the methyl alcohol of sodium methylate.There is transesterification reaction, form the methyl esters of trichlorogalacto-sucrose and acid, such as, when trichlorogalacto-sucrose-6-ester is trichlorogalacto-sucrose-6-acetic ester, form methyl acetate.The methyl esters of described acid is by distillation removing.
industrial applicability
The method of the invention is useful in the preparation of trichlorogalacto-sucrose.Trichlorogalacto-sucrose is a kind of high intensity sweetner, can be used in numerous food product and beverage application and other application.These application comprise, such as: beverage, combination sweetener, the consumer's goods, sweeting agent goods, label (Luber, U.S.Pat.No.6,277,409), pharmaceutical composition (Luber, U.S.Pat.No.6,258,381, Roche, U.S.Pat.No.5,817,340, and McNally, U.S.Pat.No.5, 593, 696), liquid composition (the Gelotte of rapid absorption, U.S.Pat.No.6, 211, 246), stable foam composition (Gowan, Jr., U.S.Pat.No.6, 090, 401), dental floss (Ochs, U.S.Pat.No.6, 080, , 481), pharmaceutical dosage form (Gowan cracked fast, Jr., U.S.Pat.No.5, 876, 759), for the beverage concentrates (Shah of medical purpose, U.S.Pat.No.5, 674, 522), aqeous suspension (the Ratnaraj of medicine, U.S.Pat.No.5, 658, 919, Gowan, Jr.U.S.Pat.Nos.5,621,005 and 5,374,659, and Blase, U.S.Pat.Nos.5,409,907 and 5,272,137), fruit spreads (Antenucci, U.S.Pat.No.5,397,588, and Sharp, 5,270,071), liquid concentrating composition (Antenucci, U.S.Pat.No.5,384,311) and stable sorbic acid solutions (Merciadez, U.S.Pat.No.5,354,902).Multiple standards well known in the art " taste test " scheme that the determination of acceptable sweeting agent is known by this area scientific and technical personnel completes, and such as, reference is at Merkel, U.S.Pat.No.6,998,144 and Shamil, U.S.Pat.No.6,265, the scheme described in 012.
Advantageous property of the present invention is by observing with reference to following embodiment, and described embodiment illustrates but do not limit the present invention.
Embodiment
Nomenclature
DMFN, dinethylformamide
DSDA1,3-diacetoxy-1,1,3,3-tetrabutyldistannoxane (distannoxane diacetate esters); (C
4h
9)
2sn (OAc)-O-Sn (OAc) (C
4h
9)
2
embodiment 1
This example demonstrates method of the present invention.
25.67g sucrose and 550.0gDMF are added in the flask of 1 liter, and dissolve sucrose dissolved at 80 DEG C.After sucrose dissolved, 52.07gDSDA is added.Utilize rotatory evaporator, in bath temperature 80 DEG C by water and DMF condistillation about 1 hour.Final condition in flask is about 70 DEG C and 40mmHg (5.3kPa).The product obtained is the light yellow oil of about 124.48g.
By described product 22.0g hexanaphthene dilution, thus in acetylation step, help tin compound to keep in the solution, and utilize 9.22g diacetyl oxide 2-3 DEG C of acetylize.Obtain sample and analyzed by high pressure lipuid chromatography (HPLC).When 90 minutes, described reaction mixture comprises cane sugar-6-acetic ester (15.23%; Be 88.65% after normalization method), diacetate esters (1.15%; Be 6.69% after normalization method), other monoacetate (0.406%; Be 2.47% after normalization method) and sucrose (0.377%; Be 2.19% after normalization method).These results illustrate, reaction very rapidly completes.Product after final quencher is the almost colourless solution not decomposing sign as seen.
embodiment 2
This example demonstrates the method which using low temperature dewatering.
25.67g sucrose and 400gDMF are added in the flask of 1 liter.At 80 DEG C by sucrose dissolved.After sucrose dissolved, 48.26gDSDA is added.Utilize rotatory evaporator, in bath temperature 15 DEG C by water and DMF condistillation about 1 hour.Final condition in flask is about 10 DEG C and < 1mmHg (< 0.1kPa).The product of this step is the water white oil of about 173.7g.
By the dilution of described product 22.0g hexanaphthene, thus in acetylation step, tin compound is kept in the solution, and utilize 9.19g diacetyl oxide lower than 5 DEG C of acetylizes.Obtain sample and analyzed by high pressure lipuid chromatography (HPLC).When 60 minutes, described reaction mixture comprises cane sugar-6-acetic ester (13.22%; Be 83.1% after normalization method), diacetate esters (0.84%; Be 5.3% after normalization method), other monoacetate (0.59%; Be 3.7% after normalization method) and sucrose (1.25%; Be 7.9% after normalization method).When 135 minutes, described reaction mixture comprises cane sugar-6-acetic ester (13.42%; Be 84.9% after normalization method), diacetate esters (1.20%; Be 7.6% after normalization method), other monoacetate (0.63%; Be 4.0% after normalization method) and sucrose (0.549%; Be 3.5% after normalization method).Product after final quencher is the colourless solution not decomposing sign as seen.
embodiment 3
This example demonstrates the method which using low temperature dewatering.
25.67g sucrose and 550.0gDMF are added in the flask of 1 liter.At 78 DEG C by sucrose dissolved.After sucrose dissolved, 52.0gDSDA is added.Utilize rotatory evaporator, in bath temperature 60 DEG C by water and DMF condistillation about 1 hour.Final condition in flask is about 50 DEG C and absolute 15mmHg (2.0kPa).The product of this step is the light yellow oil of 167.43g.
By the dilution of described product 22.0g hexanaphthene, thus in acetylation step, tin compound is kept in the solution, and utilize 9.19g diacetyl oxide lower than 5 DEG C of acetylizes.Obtain sample and analyzed by high pressure lipuid chromatography (HPLC).1 is constantly little, and described reaction mixture comprises cane sugar-6-acetic ester (14.87%; Be 87.8% after normalization method), diacetate esters (1.21%; Be 7.0% after normalization method), other monoacetate (0.50%; Be 3.0% after normalization method) and sucrose (0.36%; Be 2.1% after normalization method).1.5 is constantly little, and described reaction mixture comprises cane sugar-6-acetic ester (14.83%; Be 87.4% after normalization method), diacetate esters (1.45%; Be 8.6% after normalization method), other monoacetate (0.50%; Be 3.1% after normalization method) and sucrose (0.16%; Be 0.9% after normalization method).Product after final quencher is the almost colourless solution not decomposing sign as seen.
embodiment 4
This example demonstrates and which use the acetylizad method of low temperature.
25.67g sucrose and 301.42gDMF are added in the flask of 1 liter.Dissolve sucrose dissolved at 80 DEG C.After sucrose dissolved, 48.30gDSDA is added.Utilize rotatory evaporator, in bath temperature 80 DEG C by water and DMF condistillation about 1 hour.Final condition in flask is about 70 DEG C and absolute 40mmHg (5.3kPa).The product of this step is the light yellow oil of about 164.39g.
By described product 22.0g hexanaphthene dilution, thus in acetylation step, this compound is kept in the solution, and utilize the acetylize below-20 DEG C of 9.19g diacetyl oxide.Obtain sample and analyzed by high pressure lipuid chromatography (HPLC).After 1 hour, described reaction mixture comprises cane sugar-6-acetic ester (12.83%; Be 78.1% after normalization method), diacetate esters (0.591%; Be 3.5% after normalization method), other monoacetate (0.46%; Be 2.7% after normalization method) and sucrose (2.64%; Be 15.7% after normalization method).After 4 hours, described reaction mixture comprises cane sugar-6-acetic ester (15.84, be 87.2% after normalization method), diacetate esters (1.26, be 6.9% after normalization method), other monoacetate (0.54, be 3.0% after normalization method) and sucrose (0.53, be 2.9% after normalization method).These results illustrate, compared with high temperature acetylation, this reaction is comparatively slow, but completes similarly.Product after final quencher is the almost colourless solution not decomposing sign as seen.
embodiment 5
This example demonstrates the solvent which uses minimizing and in acetylize, employ the method for the sucrose-tin adduct of high ultimate density.
25.67g sucrose and 220.0gDMF are added in the flask of 1 liter.At 80 DEG C by sucrose dissolved.After sucrose dissolved, 48.36gDSDA is added.Utilize rotatory evaporator, in bath temperature 80 DEG C by water and DMF condistillation about 0.75 hour.Final condition in flask is about 70 DEG C and 35mmHg (about 4.7kPa).Product is the yellow oil of about 94.20g.
By described product 17.5g dry DMF and the dilution of 22.0g hexanaphthene, thus in acetylation step, this compound is kept in the solution.Utilize 9.19g diacetyl oxide by product lower than 5 DEG C of acetylizes.Obtain sample and analyzed by high pressure lipuid chromatography (HPLC).After 1 hour, described reaction mixture comprises cane sugar-6-acetic ester (23.75%; Be 87.0% after normalization method), diacetate esters (2.19%; Be 7.9% after normalization method), other monoacetate (0.71%; Be 2.7% after normalization method) and sucrose (0.68%; Be 2.5% after normalization method).After 1.5 hours, described reaction mixture comprises cane sugar-6-acetic ester (23.34%; Be 86.6% after normalization method), diacetate esters (2.55%; Be 9.2% after normalization method), other monoacetate (0.69%; Be 2.6% after normalization method) and sucrose (0.42%; Be 1.5% after normalization method).Product after final quencher is the almost colourless solution not decomposing sign as seen.
embodiment 6
This example demonstrates and wherein do not add solubility promoter and assist acetylizad method.
25.67g sucrose and 250.0gDMF are added in the flask of 1 liter.At 80 DEG C by sucrose dissolved.After sucrose dissolved, 48.25gDSDA is added.Utilize rotatory evaporator, in bath temperature 80 DEG C by water and DMF condistillation about 30 minutes.Final condition in flask is about 70 DEG C and 40mmHg (5.3kPa).The product obtained is the light yellow oil of about 119.09g.
By described product utilization 9.19g diacetyl oxide lower than 5 DEG C of acetylizes.Obtain sample and analyzed by high pressure lipuid chromatography (HPLC).After 1 hour, described reaction mixture comprises cane sugar-6-acetic ester (20.80%; Be 87.6% after normalization method), diacetate esters (2.00%; Be 8.42% after normalization method), other monoacetate (0.67%; Be 2.80% after normalization method) and sucrose (0.29%; Be 1.2% after normalization method).These results illustrate, reaction very rapidly completes.Product after final quencher is the almost lurid solution not decomposing sign as seen.
embodiment 7
This example demonstrates the method wherein using not solvent-laden DSDA in dehydration.
48.25gDSDA (containing 15% hexanaphthene of having an appointment to keep liquid) is added in the flask of 1 liter.By being heated to 80 DEG C of removing hexanaphthenes, and by vacuum drop to 40mmHg.Add the 25.67g sucrose be dissolved in 302.98gDMF wherein.Utilize rotatory evaporator, in bath temperature 80 DEG C by water and DMF condistillation about 30 minutes.Final condition in flask is about 70 DEG C and 40mmHg (5.3kPa).The product obtained is the light yellow oil of 160.69g.
By described product utilization 9.19g diacetyl oxide lower than 5 DEG C of acetylizes.Obtain sample and analyzed by high pressure lipuid chromatography (HPLC).After 1 hour, described reaction mixture comprises cane sugar-6-acetic ester (14.61%; Be 87.2% after normalization method), diacetate esters (1.18%; Be 7.0% after normalization method), other monoacetate (0.57%; Be 3.4% after normalization method) and sucrose (0.39%; Be 2.3% after normalization method).These results illustrate, reaction very rapidly completes.Product after final quencher be do not decompose sign as seen be almost lurid solution.
Content disclosed by the invention comprises appended claim.After describing invention, our present claimed appended claim and equivalents thereto thereof.
Claims (18)
1., for the production of a method for sucrose-6-ester, described method comprises the following steps: in order
A () provides the first reaction mixture, described first reaction mixture comprises sucrose, polar aprotic solvent and organic tin acylation promoter;
(b) from described first reaction mixture except anhydrating, to provide substantially water-free second reaction mixture; And
C () adds carboxylic acid anhydride in described second reaction mixture, to provide the 3rd reaction mixture, thus prepare sucrose-6-ester;
Wherein:
Non-polar co-solvent is not added to described reaction mixture in step (b) period; And
In step (b), temperature is no more than 80 DEG C.
2. method according to claim 1, wherein, in step (b) period, the removing of water is undertaken by under reduced pressure being distilled together with described polar aprotic solvent by water.
3. method according to claim 1, wherein, described first reaction mixture and/or described second reaction mixture are made up of sucrose, described polar aprotic solvent, described organic tin acylation promoter and/or their reaction product substantially.
4. method according to claim 1, wherein, in step (c) period, keeps described 3rd reaction mixture the time period being enough to prepare described sucrose-6-ester below 10 DEG C.
5. method according to claim 1, wherein, the temperature in step (b) is between 80 DEG C to 20 DEG C.
6. method according to claim 1, wherein, the temperature in step (b) is between 78 DEG C to 30 DEG C.
7. method according to claim 1, wherein, the temperature in step (b) is between 75 DEG C to 40 DEG C.
8. method according to claim 1, wherein, the temperature in step (b) is between 70 DEG C to 50 DEG C.
9. method according to claim 1, wherein, described polar aprotic solvent is DMF.
10. method according to claim 1, wherein, described organic tin acylation promoter is 1,3-bis-(acyloxy)-1,1,3,3-tetra--(alkyl) distannoxane.
11. methods according to claim 1, wherein, described organic tin acylation promoter is 1,3-diacetoxy-1,1,3,3-tetrabutyldistannoxane.
12. methods according to claim 1, wherein, described organic tin acylation promoter is 1-acyloxy-3-hydroxyl-1,1,3,3-tetra--(alkyl) distannoxane.
13. methods according to claim 12, wherein, described organic tin acylation promoter is 1-acetoxy-3-hydroxyl-1,1,3,3-tetrabutyldistannoxane.
14. methods according to claim 1, wherein, described carboxylic acid anhydride is diacetyl oxide and described sucrose-6-ester is cane sugar-6-acetic ester.
15. methods according to claim 1, wherein, described carboxylic acid anhydride is benzoyl oxide and described sucrose-6-ester is Sucrose-6-benzoate.
16. methods according to claim 1, wherein, described method is batch processes.
17. methods according to claim 1, wherein, described method is continuation method.
18. according to the method for any one described in front claim, and described method also comprises: after step (c), described sucrose-6-ester is converted into one or more additional steps of trichlorogalacto-sucrose.
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| PCT/GB2010/001904 WO2011045566A1 (en) | 2009-10-12 | 2010-10-12 | Low temperature, single solvent process for the production of sucrose-6-ester |
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| GB201110520D0 (en) * | 2011-05-10 | 2011-08-03 | Tate & Lyle Technology Ltd | Extraction of carboxylic acids with tin compounds |
| CN104098617A (en) * | 2013-04-08 | 2014-10-15 | 南京工业大学 | Preparation method of sucrose-6-acetate |
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| GB2539112B (en) | 2013-12-16 | 2020-11-04 | Tate & Lyle Tech Ltd | Chlorination of sucrose-6-esters |
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- 2010-10-12 WO PCT/GB2010/001904 patent/WO2011045566A1/en active Application Filing
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- 2010-10-12 EP EP10766092A patent/EP2488541A1/en not_active Withdrawn
- 2010-10-12 KR KR1020127012141A patent/KR20120089718A/en not_active Application Discontinuation
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106349300A (en) * | 2016-08-30 | 2017-01-25 | 安徽金禾实业股份有限公司 | Method for reaction of sucralose esterified single solvent |
| CN106349300B (en) * | 2016-08-30 | 2019-02-26 | 安徽金禾实业股份有限公司 | Sucralose is esterified single solvent reaction method |
Also Published As
| Publication number | Publication date |
|---|---|
| GB2474311B (en) | 2012-10-17 |
| CN102639550A (en) | 2012-08-15 |
| US8921540B2 (en) | 2014-12-30 |
| GB2474311A (en) | 2011-04-13 |
| GB0920385D0 (en) | 2010-01-06 |
| JP2013507349A (en) | 2013-03-04 |
| IE20100653A1 (en) | 2011-05-11 |
| JP5726195B2 (en) | 2015-05-27 |
| IE86139B1 (en) | 2013-02-27 |
| US20110087018A1 (en) | 2011-04-14 |
| WO2011045566A1 (en) | 2011-04-21 |
| KR20120089718A (en) | 2012-08-13 |
| EP2488541A1 (en) | 2012-08-22 |
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